Prof. Brendan Wren, London School of Hygiene and Tropical Medicine
fBen - Clostridium difficile, or C. diff. is a potentially lethal, often hospital-acquired infection of the gut, causing bloating, diarrhoea and abdominal pain. One strain, O27, is particularly aggressive, and has caused 50,000 cases and 5000 deaths in recent years in the UK alone. Itís often associated with a disruption of the bacteria that normally live in the gut, the gut microbiota, so can be a big problem when people are treated with broad-spectrum antibiotics.
Now, new research at the Sanger Institute in Cambridge, the University of Aberdeen and the London School of Hygiene and Tropical Medicine has identified a cocktail of bacteria which, when fed to infected mice, clears out the C. diff. Brendan Wren, from the London School of Hygiene and Tropical Medicine, is involved in the project, and he joins us now.
Brendan, thank you ever so much for joining us. So, what really is the problem with C. diff?
Brendan - Itís a fairly unusual infection in the sense that antibiotics, which we all rely on, actually end up exacerbating the disease. So, when patients are given antibiotics, it kills the good bacteria as well as the bad bacteria and it disturbs the gut microbial balance. In other words, the antibiotics are indiscriminant and under these conditions, the bacterium Clostridium difficile takes over, produces toxins and as you mentioned, it can cause death and severe diarrhoea.
Ben - So traditionally, how do we treat it?
Brendan - There are some antibiotics that can be used, but these, again, do disturb the microflora and under these conditions patients are going to become more and more ill, and they can have multiple relapses. So, itís quite a desperate chronic disease, to the extent where in some countries, people have attempted to replace the microflora with bacteria from the faeces of a patient or near relative. So this faecal transplantation has been used fairly successfully in many patients to restore the microflora and overcome Clostridium difficile infection.
Ben - Now, faecal transplant, the very idea of it, has got quite a lot of yuck factor associated with it. Was this what inspired you to look for this particular cocktail of bacteria that you found?
Brendan - Well, my colleagues at the Sanger Institute have done exactly that, but important part of the study is that this mimicked the human disease in mice and thatís allowed them to follow the disease and follow the populations of the bacteria in the gut, using the new 16S sequencing methods. This allowed them to know the relative proportions of very complex bacteria that is there and sure enough, when antibiotics are causing Clostridium difficile to take over the gut, they're able to monitor which bacteria became available as the mice recovered and ended up choosing a collection of six specific bacteria that could be used as a cocktail as a form of bacterial therapy. So now, we have a more rational approach as to restoring the gut microflora rather than using faecal transplantation.
Ben - it certainly gets over some of the yuck factor, doesnít it? What bacteria were these? Were these things we already knew about or is there something actually new to science here?
Brendan - Most of them are quite obscure and 3 of them were actually quite novel, and theyíve been fully sequenced now and can study them in far more detail. So, 3 of them were completely novel and I'm sure that there may be other bacteria out there that might be quite useful in a cocktail to help get back, to restore the normal microflora.
Ben - Now, is it something in particular about these bacteria that you think is performing the role or would it really work with any cocktail thatís the right balance of bacteria?
Brendan - I think only some bacteria would allow this for various reasons. Itís to do with competition for food and there are many different factors, but not all bacteria would be capable of doing this. So itís a form of probiotics, but itís a more rational approach, and we still have a lot to do to really understand why these in particular are good and I'm sure there's probably some others out there as well.
Ben - So, what's going to be the next step? Presumably, we can't just use the same bacteria because these are from mice, but can we apply the same sort of techniques to looking at the human gut microbiota and trying to work out if there are key microbes that we can then Ė as you said Ė put into a probiotic that we then use to treat C. diff?
Brendan - Yes, thatís what weíre doing currently with a new MRC £3million grant and weíre looking at patients who come in to hospital before, after and during infection, then during reinfection. And using the new sequencing techniques weíll follow all the bacteria thatís in the gut and work out an ideal combination that would allow rational bacteria therapy.
Ben - Now they say that your gut microbiota is as unique to you as your fingerprint. Does this mean that actually weíll have to work out a new cocktail for each person or in the mice, did you find that actually, there were these core bacteria that worked for every mouse you tested?
Brendan - At the moment, it did seem to work in most mice, but again, we won't know what will happen in humans. But there are some general species that we have great hope for and although people do have individual microbes, a thousand or so species, the point is that some of these would be particularly good at growing and counteracting the effect of competition with Clostridium difficile.